Spleen stiffness in patients with chronic liver disease evaluated by 2-D shear wave elastography with ultrasound multiparametric imaging.

BACKGROUND: The novel 2-D shear wave elastography (2D-SWE) can measure two ultrasound parameters: shear wave dispersion (SWD) and shear wave speed (SWS). We investigated the ability of 2D-SWE in measuring spleen stiffness using ultrasound multiparametric imaging. METHODS: This cross-sectional study included patients with chronic liver disease who underwent esophagogastroduodenoscopy and ultrasonographic examinations of the spleen between September 2018 and December 2021. In total, 157 patients were enrolled in this study: 81 and 67 patients were included in the pilot set for hepatic venous pressure gradient (HVPG) measurements and validation cohort without HVPG measurements, respectively. To confirm reproducibility between the two examiners, an additional 30 patients were enrolled. RESULTS: The Bland-Altman plots revealed no significant bias in the SWD as measured by two examiners. The splenic SWS (r = 0.752) and SWD (r = 0.444) were correlated with the HVPG. Regarding high-risk varices, as per the Youden index, the cut-off value for splenic SWS was 3.30 m/s, with a sensitivity of 85.7%, specificity of 92.5%, positive predictive value of 85.7%, and negative predictive value of 92.4% in the pilot set. In the validation set, good diagnostic performance by the splenic SWS was observed. However, SWD did not perform as well as SWS. CONCLUSIONS: The splenic SWS, measured using ultrasound multiparametric imaging, was closely correlated with the HVPG. Thus, SWS is a useful predictive marker for high-risk varices.

Clinical significance of high monocyte counts for the continuous treatment with nintedanib.

BACKGROUND: Nintedanib is now widely used to treat interstitial lung disease (ILD). Adverse events, which occur in not a few patients, make it difficult to continue nintedanib treatment, but the risk factors for adverse events are not well understood. METHODS: In this retrospective cohort study, we enrolled 111 patients with ILDs treated with nintedanib and investigated the factors involved in starting dosage reduction, withdrawal, or discontinuation within 12 months, even with appropriate symptomatic treatment. We also examined the efficacy of nintedanib in reducing the frequency of acute exacerbations and the prevention of pulmonary function reduction. RESULTS: Patients with high monocyte counts (> 0.454 × 109/L) had a significantly higher frequency of treatment failure, such as dosage reduction, withdrawal, or discontinuation. High monocyte count was as significant a risk factor as body surface area (BSA). Regarding efficacy, there was no difference in the frequency of acute exacerbations or the amount of decline in pulmonary function within 12 months between the normal (300 mg) and reduced (200 mg) starting dosage groups. CONCLUSION: Our study results indicate that patients with higher monocyte counts (> 0.454 × 109/L) should very careful about side effects with regard to nintedanib administration. Like BSA, a higher monocyte count is considered a risk factor for nintedanib treatment failure. There was no difference in FVC decline and frequency of acute exacerbations between the starting doseage of nintedanib, 300 mg and 200 mg. Considering the risk of withdrawal periods and discontinuation, a reduced starting dosage may be acceptable in the patients with higher monocyte counts or small body sizes.

Measurement of multiple spleen lengths is not necessary for non-invasive prediction of high-risk esophagogastric varices.

AIM: To validate an appropriate spleen size measurement technique for the prediction of high-risk esophagogastric varices. METHODS: This retrospective cross-sectional study included 369 patients who underwent ultrasonography and computed tomography (CT) of the spleen and esophagogastroduodenoscopy between January 2018 and December 2020. Maximum spleen length, width, and craniocaudal length were measured in a longitudinal view. The two-dimensional (2D) spleen index (maximum length × maximum width in the longitudinal view) was calculated. A three-dimensional (3D) spleen index was then defined as follows: 2D spleen index × maximum length in the transverse view. The similarity in spleen volume measured by CT and ultrasonography (spleen index) was assessed by the correlation coefficient. The diagnostic accuracies of the spleen index, platelet/spleen length, and platelet/spleen index were calculated to determine the overall diagnostic accuracy. RESULTS: Compared to the other spleen indices, our 3D spleen index was significantly better correlated with spleen volume on CT (r = 0.91, 95% confidence interval 0.89-0.92, p < 0.001). Receiver-operating characteristic curve analyses revealed no significant difference between the 3D and 2D indices (p = 0.228) but did show a significant difference between the 3D and one-dimensional indices (p = 0.020). Although the area under the curve for the platelet count combined with the spleen index or length was higher than that for our 3D index, there was no significant difference between platelet count and spleen index or length (p = 0.078). CONCLUSIONS: Platelet/spleen length has a reasonable ability to predict high-risk esophagogastric varices, even though measurement of two or three factors can be correlated with spleen volume.

Validation of the FibroScan-aspartate aminotransferase score by vibration-controlled transient and B-mode ultrasound elastography.

AIM: The FibroScan-aspartate aminotransferase (FAST) score comprises an easy and feasible method for identifying advanced non-alcoholic steatohepatitis. Recently, shear-wave elastography and attenuation coefficient measurement on B-mode ultrasound (US) have become widely utilized. We investigated the diagnostic accuracy of the FAST score as calculated using US-elastography compared with that using vibration-controlled transient elastography (VCTE). METHODS: Patients with chronic liver disease who underwent VCTE, point-shear-wave elastography with attenuation coefficient measurement, and liver biopsy on the same day between January 2015 and September 2020 were retrospectively reviewed. RESULTS: Of 189 patients, 94 underwent VCTE using both M and XL probes. The C-statistics were similar for VCTE (0.846) and US-elastography (0.814; p = 0.251), and for M (0.857) and XL probes (0.833; p = 0.412). Scatter and Bland-Altman plots showed good reproducibility for the FAST score. For VCTE, a cut-off of ≤0.35 had a sensitivity of 92.3%, negative predictive value of 85.5%, and negative likelihood ratio of 0.14, and a cut-off of ≥0.67 had a specificity of 90.6%, positive predictive value of 88.1%, and positive likelihood ratio of 6.03, for ruling out and in advanced non-alcoholic steatohepatitis, respectively. For US-elastography, a cut-off of ≤0.35 had a sensitivity of 90.4%, negative predictive value of 83.3%, and negative likelihood ratio of 0.16, and a cutoff of ≥0.67 had a specificity of 91.8%, positive predictive value of 85.1%, and positive likelihood ratio of 4.67, for ruling out and in advanced non-alcoholic steatohepatitis, respectively. CONCLUSIONS: The FAST score is highly reproducible, even when different echo equipment or probes are used.

Calponin expression in renal tubulointerstitial fibrosis induced in rats by Cisplatin.

Renal tubulointerstitial fibrosis is the common feature of chronic renal failure, regardless of its etiology. Myofibroblasts play important roles in progression of the fibrosis and are characterized by expressions of various cytoskeletons such as vimentin, desmin and α-smooth muscle actin (α-SMA). To pursue the characteristics of the cells, we immunohistochemically investigated the relationship between calponin (a marker of terminal smooth muscles) expression and myofibroblasts in cisplatin-induced rat renal tubulointerstitial fibrosis. Calponin-expressing interstitial cells increased with fibrosis and reacted simultaneously to vimentin or α-SMA (a marker of well-differentiated myofibroblasts) but not desmin or Thy-1 (a marker of myofibroblasts at the early stage). The present study shows that calponin may be expressed transiently in relatively well-developed myofibroblasts in rat renal fibrosis. Calponin could become a marker for myofibroblast development in chronic renal toxicity in rats.

Hepatocellular Carcinoma Showing Tumor Shrinkage Due to an Abscopal Effect.

We herein report a 63-year-old man who presented with left lower jaw pain and was diagnosed with hepatocellular carcinoma with bone metastases post-examination. All tumors grew after immunotherapy with atezolizumab and bevacizumab, and his jaw pain worsened. After palliative radiation therapy, however, the tumors shrank markedly, with no recurrence seen after stopping immunotherapy. To our knowledge, this is the first case in which a radiotherapy- and immunotherapy-mediated abscopal effect facilitated tumor shrinkage and immunotherapy discontinuation.

Obesity may be a risk factor for transbronchial lung cryobiopsy-related adverse events in Japanese patients with interstitial lung disease.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) is known to be associated with a high incidence of adverse events. However, few studies have investigated the correlation between obesity and the risk of TBLC-related adverse events, especially in Asians, who are known to have characteristic differences in height and weight as compared to individuals of other ethnicities. METHODS: We retrospectively assessed 102 Japanese patients who underwent TBLC for the diagnosis of interstitial lung disease to evaluate the correlation between patient characteristics and the occurrence of TBLC-related adverse events (hemorrhage, pneumothorax, and acute exacerbation of interstitial lung disease). RESULTS: TBLC-related adverse events occurred in 19 patients (18.6 %), with hemorrhage being the most common adverse event (in 14 patients, 13.7 %). There was no correlation between age, sex, or pulmonary function test results and the occurrence of adverse events. The body mass index (BMI) cut-off predicting the occurrence of all adverse events was 26.6 kg/m2 (sensitivity of 0.389 and specificity of 0.852), and that predicting the occurrence of adverse events of hemorrhage was 26.8 kg/m2 (sensitivity of 0.462 and specificity of 0.907). Among patients with a BMI >26.8 kg/m2, adverse events of hemorrhage occurred in 37.5 % of cases, which was higher than among those with a BMI <26.8 kg/m2. CONCLUSIONS: Obesity is a risk factor for the incidence of TBLC-related adverse events, particularly adverse events of hemorrhage, in Japanese patients. The BMI cut-off values that predicted an increased frequency of TBLC-related adverse events and hemorrhage specifically were 26.6 and 26.8 kg/m2, respectively.

A case of hepatocellular carcinoma with pseudoaneurysm formation upon lenvatinib administration.

A 79-year-old man received treatment for multiple intrahepatic hepatocellular carcinoma with atezolizumab + bevacizumab. However, he developed lower back pain attributed to spinal metastases upon tumor enlargement; thus, he was admitted to our hospital for a change from atezolizumab + bevacizumab to lenvatinib and radiation therapy for the spinal metastases. On the 11th day after starting lenvatinib treatment, a pulsatile aneurysm appeared in the tumor, detected using abdominal ultrasonography Micro B-flow imaging, which visualized blood flow at a high frame rate; this was diagnosed as a pseudoaneurysm. The patient refused treatment for the pseudoaneurysm; therefore, he was carefully followed up. Fortunately, the pseudoaneurysm disappeared on the 17th day. One month later, the tumor had become completely necrotic. Lenvatinib demonstrated effectiveness in inhibiting angiogenesis in the tumor, as evidenced by a decrease in tumor blood flow. This case report suggests that pseudoaneurysm formation within the tumor occurs early after the administration of lenvatinib; thus, clinicians must be aware of the potential risk of pseudoaneurysm rupture.

Diagnostic accuracy of ultrasound-derived fat fraction for the detection and quantification of hepatic steatosis in patients with liver biopsy.

PURPOSE: This retrospective study was conducted to investigate the diagnostic accuracy of ultrasound-derived fat fraction (UDFF) for grading hepatic steatosis using liver histology as the reference standard. METHODS: Seventy-three patients with liver disease were assessed using UDFF and liver biopsy. Pearson's test and the Bland-Altman plot were used to assess the correlation between UDFF and histological fat content in liver sections. The UDFF cutoff values for histologically proven steatosis grades were determined using the area under the receiver operating characteristic curve (AUROC). RESULTS: The median age of the patients was 66 (interquartile range 54-74) years, and 33 (45%) were females. The UDFF values showed a stepwise increase with increasing steatosis grade (p < .001) and were strongly correlated with the histological fat content (r = .7736, p < .001). The Bland-Altman plot revealed a mean bias of 2.384% (95% limit of agreement, - 6.582 to 11.351%) between them. Univariate regression analysis revealed no significant predictors of divergence. The AUROCs for distinguishing steatosis grades of ≥ 1, ≥2, and 3 were 0.956 (95% confidence interval [CI], 0.910-1.00), 0.926 (95% CI, 0.860-0.993), and 0.971 (95% CI, 0.929-1.000), respectively. The UDFF cutoff value of > 6% had a sensitivity and specificity of 94.8% and 82.3%, respectively, for diagnosing steatosis grade ≥ 1. There was no association between UDFF and the fibrosis stage. CONCLUSION: UDFF shows strong agreement with the histological fat content and excellent diagnostic accuracy for grading steatosis. UDFF is a promising tool for detecting and quantifying hepatic steatosis in clinical practice.

Interleukin-1ß plays key roles in LPA-induced amplification of LPA production in neuropathic pain model.

Lysophosphatidic acid (LPA) is a bioactive lipid mediator that exerts a wide range of biological actions. In recent decades, LPA has been demonstrated as an important initiator of neuropathic pain based on the mechanisms of LPA-induced feed-forward LPA amplification. In this study, we examined the possible involvement of interleukin (IL)-1ß in such LPA production. Intrathecal (i.t.) LPA injection rapidly increased the expression of IL-1ß mRNA in the spinal dorsal horn as early as 0.5 h after injection, and the level reached peak at 2 h. Through a developed quantitative mass spectrometry for detecting LPA species, the elevated levels of 18:1, 16:0, and 18:0 LPA in the spinal dorsal horn were observed at 3 h after 18:1 LPA injection and this elevation was completely blocked by the pretreatment of IL-1ß-neutralizing antibody. Moreover, enzyme assay experiments showed that LPA (i.t.) significantly activated calcium-independent phospholipase A2 (iPLA2) and cytosolic phospholipase A2 (cPLA2) in the spinal dorsal horn at 1 and 2 h, respectively, and these biochemical changes were also significantly inhibited by IL-1ß-neutralizing antibody. Similarly, IL-1ß-neutralizing antibody reversed LPA-induced neuropathic pain-like behavior. These findings suggest that the early release of IL-1ß is involved in LPA-induced amplification of LPA production, which underlies the initial mechanisms of LPA-induced neuropathic pain.

Metastasis from Renal Cell Carcinoma to Ectopic Pancreas Diagnosed after Resection.

We herein report a 68-year-old man who underwent nephrectomy for right renal cell carcinoma 10 years prior. He remained under regular medical observation, and abdominal computed tomography showed tumors in the head and tail of the pancreas. He was diagnosed with pancreatic metastasis from renal cell carcinoma. He underwent surgical excision. The pathologic diagnosis proved that the pancreatic tumors were metastases from renal cell carcinoma and clarified that an ectopic pancreas in the duodenum had metastases as well. To our knowledge, this is the first case of metastasis to an ectopic pancreas.

B-mode shear wave elastography can be an alternative method to vibration-controlled transient elastography according to a moderate-scale population study.

PURPOSE: We aimed to compare vibration-controlled transient elastography (VCTE) with shear wave elastography (SWE) without previous analysis and generate regression equations between VCTE and new point SWE using combination-elastography. METHODS: Overall, 829 patients with chronic liver disease were enrolled in this study. Patients with a skin-liver capsule distance > 25 mm were excluded. The reproducibility of VCTE and SWE was confirmed in a phantom study and a clinical study. Considering that combination-elastography allows measurement based on strain elastography, a similar analysis was performed for the liver fibrosis index (LFI), which is a quantitative value for evaluation of liver fibrosis calculated using strain elastography image features. Regression equations between the VCTE and SWE values were obtained based on linear regression analysis. RESULTS: In the phantom study and clinical study, there was a strong correlation between VCTE and SWE [r = 0.995 (p < 0.001) and r = 0.747 (p < 0.001), respectively). The regression equation between VCTE and SWE was VCTE (kPa) = 1.09 × point SWE (kPa) - 0.17. The Bland-Altman plots revealed no statistically significant bias. Meanwhile, there was no correlation between VCTE and LFI (r = 0.279). There was a statistically significant bias between VCTE and LFI in the Bland-Altman plots. The inter-operator reliability showed a good intraclass correlation coefficient of 0.760 (95% confidence interval: 0.720-0.779). CONCLUSION: Liver stiffness measured using point SWE was comparable to that measured using VCTE.

Deep attenuation transducer to measure liver stiffness in obese patients with liver disease.

PURPOSE: Deep attenuation transducers (DAX) are capable of imaging at diagnostic depths of up to 40 cm. The feasibility of DAX for liver stiffness measurement (LSM) has not been reported clinically. We aimed to assess the feasibility and reliability of DAX for LSM. METHODS: Overall, 219 patients with chronic liver disease were enrolled. The success rate (acquired after ≥ 10 valid measurements) and inadequate measurements (interquartile range/median ≥ 0.3) for DAX were compared with those of conventional convex (c-convex) probes and M and XL probes of vibration-controlled transient elastography. RESULTS: LSM was successfully performed for all patients using DAX through all degrees of skin-to-liver capsular distance (SCD). Especially in patients with an SCD ≥ 30 mm, the difference in the rate of acquisition of 10 valid measurements was remarkable: M probe (8/33, 24.2%), XL probe (26/33, 78.8%), c-convex probe (33/43, 76.7%), and DAX (44/44, 100%). In patients with an SCD ≥ 30 mm, the inadequate measurement rate of M probe (1/8, 12.5%), XL probe (8/26, 30.8%), and c-convex probe (6/33, 18.2%) was higher than that of DAX (1/43, 2.3%). The areas under the curve for diagnosis of F4 with shear wave speed by c-convex and DAX were 0.916 and 0.918, respectively. Between DAX and c-convex probes, the intraclass correlation coefficient of 0.937 (95% CI 0.918-0.952) was excellent. Bland-Altman plots revealed that there was no statistically significant bias. CONCLUSION: Liver stiffness measured by DAX is feasible and reliable for all patient populations, while the XL probe is limited to use in obese patients.

Lymphatic drainage dysfunction via narrowing of the lumen of cisterna chyli and thoracic duct after luminal dilation.

BACKGROUND: The chronological pattern of extrahepatic lymphatic vessel progression in the course of chronic liver disease has not been clarified. This study aimed to clarify the chronological changes in lymphatic vessels with liver disease progression. METHODS: This was a prospective cross-sectional study that enrolled a total of 199 patients. The maximum diameter of the cisterna chyli (CC) or terminal thoracic duct (tTD) was measured using computed tomography or ultrasonography, respectively. Changes in the maximum diameters of the CC and tTD were evaluated with patients with chronic liver disease as the pilot set (n = 138). Subsequently, we examined whether CC/tTD could be used to re-allocate unclassified patients by the Baveno-VII criteria to appropriately diagnose clinically significant portal hypertension (CSPH) in the pilot and validation sets. RESULTS: In the pilot set, a scatter-plot showed that both CC and tTD were narrowed as terminal features in chronic liver disease after dilation. Because there was a significant correlation between the CC diameter and hepatic venous pressure gradient (r = 0.724) in unclassified patients, the diagnostic value of CC and tTD for CSPH was good (AUC: 0.961 and 0.913, respectively). After re-allocation, 68 and 27 unclassified patients were reduced to 4 and 5 in the pilot and validation sets, respectively. CONCLUSION: Both the CC and tTD narrow in the course of liver disease after dilation. Moreover, the maximum diameter of the CC and tTD can be used to re-allocate patients who are unclassified according to the Baveno-VII criteria. CLINICAL TRIAL NUMBER: UMIN trial no. 000044857.

Survival Improvements in Advanced Hepatocellular Carcinoma with Sequential Therapy by Era.

Treatment modalities for advanced hepatocellular carcinoma (HCC) have changed dramatically, with systemic therapy as the primary option. However, the effect of sequential treatment on prognosis remains unclear. This retrospective study included patients who began systemic therapy between 2009 and 2022. The patients were separated into three groups according to systemic therapy commencement. The number of therapy lines, treatment efficacy, and overall survival (OS) were compared. Multivariate analyses of the prognostic factors were analyzed using the Cox proportional hazards model. Overall, 336 patients were included (period 1: 2009-2013, n = 86; period 2: 2014-2018, n = 132; period 3: 2019-2022, n = 118). A significant etiological trend was observed with decreasing viral hepatitis-related HCC and increasing non-viral hepatitis-related HCC. Across periods 1-3, the proportion of patients who were administered >2 lines progressively increased (1.2%, 12.9%, and 17.0%, respectively; p < 0.001) and the median OS was significantly prolonged (14.3, 16.8, and 31.0 months; p < 0.001). The use of <3 lines, the non-complete and partial response of the first line, modified albumin-bilirubin at grade 2b or 3, an intrahepatic tumor number ≥ 5, extrahepatic metastasis, and alpha-fetoprotein at ≥400 ng/mL were the strongest factors associated with shorter OS. Sequential therapies have contributed to significant improvements in HCC prognosis, suggesting that sequential treatment post-progression is worthwhile for better survival.

A case of walled-off necrosis extending into the pelvic cavity successfully treated by endoscopic necrosectomy using a lumen-apposing metal stent.

A 31-year-old man developed massive walled-off necrosis extending into the pelvic cavity following severe acute alcoholic pancreatitis. Endoscopic ultrasound-guided fistula drainage was performed using a lumen-apposing metal stent, but this was insufficiently effective, and endoscopic necrosectomy was also performed, after which the patient improved. Percutaneous drainage and surgery are other options for the treatment of walled-off necrosis extending into the pelvic cavity, but a valuable case in which the patient improved with endoscopic treatment alone is presented.

Pazopanib for treating rhabdomyosarcoma in adult patients with poor performance status: A case report.

Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma usually observed in children. However, RMS rarely occurs in adults. The prognosis of adult RMS is poor and a standard chemotherapy regimen has not yet been established. Herein, we report the case of a 60-year-old Japanese woman with primary anterior mediastinal alveolar RMS (T3N0M0, stage III). The tumor increased aggressively despite first-line treatment with doxorubicin (60 mg/m2 every 3 weeks for 1 cycle) and second-line treatment with eribulin (1.4 mg/m2 every 3 weeks for 2 cycles). Although her shortness of breath and chest tightness worsened as the tumor compressed her heart and left main bronchus, and her performance status (PS) decreased to 3, third-line treatment with pazopanib (800 mg once daily) was commenced. The treatment led to suppression of tumor growth and resulted in 4-month progression-free survival. Therefore, in cases of adult RMS, considering pazopanib treatment as an option may be beneficial, even with previous ineffective treatments or poor PS.

Cisterna chyli as an optimal marker of tolvaptan response in severe cirrhotic ascites.

For patients with cirrhosis, no definitive predictor of the efficacy and prognosis of tolvaptan treatment exists. We assessed the cisterna chyli's utility as an optimal marker. We retrospectively enrolled 172 patients with cirrhosis. The effect of tolvaptan was evaluated using post-treatment survival time. The overall response to tolvaptan was 52.3%. The median cisterna chyli diameter was 4.1 mm. Of 172 patients, 100 were included in the pilot set and 72 in the validation set. According to the Youden index, the cisterna chyli diameter's cutoff value was 4 mm, with a sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of 92%, 83%, 86%, 91%, 5.43, and 0.09, respectively, in the pilot set. The area under the curve of the cisterna chyli diameter for evaluating tolvaptan's effect was 0.911 and 0.988 in the pilot and validation sets, respectively. During multivariate analysis, cisterna chyli narrowing and furosemide treatment were significant predictive factors for tolvaptan's insufficient effect. Cumulative liver transplantation-free survival rates were significantly higher in patients with cisterna chyli dilatation than in those without (p = 0.028). Our findings suggest a strong association of cisterna chyli with tolvaptan treatment response in patients with cirrhosis and hepatic edema.

Immunohistochemical characterization of macrophages and myofibroblasts in α-Naphthylisothiocyanate (ANIT)--induced bile duct injury and subsequent fibrogenesis in rats.

To investigate pathogenesis of post-bile duct (BD) injury fibrosis, interlobular BD epithelial injury was induced in male F344 rats by a single IP injection of α-naphthylisothiocyanate (75 mg/kg body weight) and rats were observed for 12 days. On days 1 to 2, cholangiocytes were injured and desquamated. On days 3 to 5, the affected BD began to regenerate, showing positive staining for CK19 and vimentin. On days 5 to 9, fibrotic areas gradually developed around regenerating BD in Glisson's sheath. These consisted of cells positive for vimentin, desmin, and α-SMA; vimentin- and desmin-positive cells were increased in early stage (days 1-3), whereas α-SMA-positive cells appeared in mid (days 4-7) and late stages (days 8-12), although there were cells coexpressing these cytoskeletons. On day 12, BD regeneration almost completed, with reduced fibrosis. Macrophages positive for ED2 (CD163) increased transiently in early stage, whereas those reacting to ED1 (CD68), OX6 (MHC II), and SRA-E5 (CD204) showed a consistent increase throughout the experiment. Interestingly, OX6-positive cells were limited to Glisson's sheath, whereas SRA-E5-positive cells were seen exclusively along sinusoids of hepatic lobules. MCP-1 mRNA increased significantly in early stage. This study shows that macrophages exhibiting different immunophenotypes and distributions participate in post-BD injury fibrosis associated with myofibroblasts expressing various mesenchymal cytoskeletons.